Research Progress on Chemical Constituents and Biological Activity of Kummerowia striata (Thunb.) Schindl.

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1. Guangxi University of Chinese Medicine, Nanning 530200, China; 2. International Zhuang Medical Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530200, China

Abstract The purpose of this paper is to review the research progress on the chemical composition and pharmacological action of Kummerowia striata (Thunb.) Schindl., so as to provide reference for the chemical research of natural medicine and the discovery of new drugs. K. striata (Thunb.) Schindl. contains a variety of active constituents, such as flavonoid glycosides, phenols and amino acids, and has a wide range of pharmacological activities, including anti-allergy, analgesia and anti-inflammation, anti-oxidation, anti-tumor and so on. It is mainly used in the folk for the treatment of cold and fever, summer-heat and dampness, vomiting and diarrhea, dysentery and so on.

Key words Kummerowia striata (Thunb.) Schindl., Chemical constituents, Pharmacological action

1 Introduction

Kummerowiastriata(Thunb.) Schindl. was first recorded in the bookMateriaMedicaforFamines. It has many different names in the folk, such as Qiabuqi, Banjiuwo, and Banjiuzuo. It is widely distributed all over the country and is the dry whole grass of the leguminous plant. When it is used for folk medicine in our country, the whole grass can be used as medicine. It grows in the fields, roadsides, mountains, hills, forests and other places. It tastes sweet, light, slightly cold, with heat-clearing and detoxification, spleen-invigorating and dampness-promoting effect. Clinically, it can be used to treat bacterial gastroenteritis, dysentery, viral hepatitis, urinary system infection, injuries from falls, cold and fever,etc.[1]. It is mainly distributed in Northeast China, Hebei, Shandong, Jiangsu, Hubei, Hunan, Fujian, Guangdong, Yunnan, Guizhou and Sichuan.K.striata(Thunb.) Schindl. is rich in resources, complex in chemical composition and widely used, so it has high research and medicinal value. By consulting a large number of research works of domestic and foreign scholars so far, this paper summarized the chemical constituents and pharmacological activities ofK.striata(Thunb.) Schindl., in order to provide direction and reference for the follow-up research and clinical application.

2 Chemical constituents

2.1FlavonoidsA large number of papers have reported thatK.striata(Thunb.) Schindl. is rich in flavonoids, amino acids, sterols and sugars. Among them, flavonoids are the important material basis for their pharmacological activities, and are closely related to the anti-inflammatory and antioxidant effects. Therefore, a clear understanding of the chemical constituents ofK.striata(Thunb.) Schindl. is very important to the study of its pharmacological effects. Five flavonoids were isolated and extracted fromK.striata(Thunb.) Schindl. by Tang Renjiu[2], and the chemical structures of the compounds were analyzed by the results of physicochemical properties and spectral data analysis. They were apigenin, quercetin, apigenin-7-O-β-D-glueopyranoside, kaempferol-3-O-β-D-glueopyranoside and apigenin-7-O-neohesperidoside, respectively. Subsequently, Li Shenghua also isolated and extracted a variety of flavonoid glycosides fromK.striata(Thunb.) Schindl., and determined the structure of 14 flavonoids, of which apigenin and quercetin were consistent with those reported by Tang Renjiu. In addition, 12 flavonoid glycosides were identified as quercetin-3-O-α-L-rhamnoside, kaempferol-3-O-α-L-rhamnoside, quercetin-3-O-β-D-galactoside, luteolin-7-O-β-D-glucoside, luteolin, kaempferol-3-O-β-D-sophoroside, isoorientin, orientin (10), apigenin-7-O-β-D-glucuronic acid methyl ester, 7-hydroxy-4′-methoxy isoflavone, medicarpin and medicarpin-7-O-β-D-glucopyranoside. The publication of these articles provides a basis for future generations to further study the material basis of the pharmacological activity and the molecular pharmacological mechanism ofK.striata(Thunb.) Schindl.

2.2SteroidsSteroids are a kind of compounds with significant physiological activities, which have significant effects in anti-tumor, anti-virus, immune regulation, treatment of cardio-cerebrovascular diseases, lowering blood sugar, lowering blood lipids and so on. Most of the compounds obtained from the modification of their parent and functional groups also have good pharmacological activities. Phytosterols are widely found in all kinds of plants. Li Wenetal.[4]isolated and extracted 14 compounds from clover, and identified them according to the physicochemical properties and spectral data of the compounds. Three different steroids were obtained, namely stigmasterol-3-O-β-D-glucopyranoside, stigmasterol and β-sitosterol. Feng Siminetal. reported the inhibitory effect of β-sitosterol and stigmasterol on acute colitis induced by DSS in mice. The results showed that stigmasterol could significantly inhibit colonic shortening, reduce the content of heme in feces, reduce the pathological score of colitis, and significantly reduce the mRNA expression levels of inflammatory factors IL-1β, IL-6, MCP-1 and cyclooxygenase COX-2 in colon tissue.β-sitosterol could also significantly reduce the pathological score of colitis and inhibit the mRNA expression levels of IL-6 and cyclooxygenase COX-2. The conclusion of this study well revealed the pharmacological mechanism ofK.striata(Thunb.) Schindl. in acute enteritis and infantile diarrhea[6-7], and provided a reasonable basis for its clinical application.

2.3AminoacidsAmino acid is one of the important nutrients that the human body needs every day. As the basic unit of protein bioactive macromolecules, protein is the material basis of life metabolism in organisms and participates in maintaining the normal life activities of cells[8].K.striata(Thunb.) Schindl. is rich in nutrients, containing a variety of amino acids and trace elements[9]. Li Nanweietal. used the dried powder ofK.striata(Thunb.) Schindl. as raw material, separated and extracted the active substances such as flavonoids, polysaccharides, amino acids and polyphenols by different methods, and studied the scavenging ability of these four active components to hydroxyl radical and DPPH free radical, so as to comprehensively evaluate the antioxidant activityinvitroofK.striata(Thunb.) Schindl. The results showed that flavonoids, polysaccharides, amino acids and polyphenols had obvious scavenging effects on DPPH free radicals and hydroxyl radicals, among which amino acids had the best antioxidant effectinvitro, and showed a significant dose-dependent relationship[10]. Although the content of amino acids inK.striata(Thunb.) Schindl. is the lowest, the amino acids are an important material basis for antioxidant activity ofK.striata(Thunb.) Schindl. and are expected to be developed into natural antioxidants and antioxidant drugs.

2.4OthersubstancesK.striata(Thunb.) Schindl. is not only rich in a variety of flavonoid glycosides and steroids, but also amino acids, phenols, and polysaccharides[11]. 70% ethanol was used for reflux extraction, and after the extract was suspended with distilled water, the polyphenols inK.striata(Thunb.) Schindl. could be separated by ethyl acetate or n-butanol extraction[12]. In addition, the content of polysaccharides in the cell wall of plant rhizome is high, which can be destroyed by enzymatic hydrolysis and acid-base extraction. Many polyphenols and plant polysaccharides have good physiological activities, but the current research on these substances is basically blank, and new active substances inK.striata(Thunb.) Schindl. need to be further studied and found.

3 Study on pharmacological activity

3.1Anti-inflammatoryeffectA large amount of literature has reported that the flavonoids inK.striata(Thunb.) Schindl. have significant anti-inflammatory and analgesic activities. Zhang Baohuietal. used 70% ethanol to extract flavonoids fromK.striata(Thunb.) Schindl., and then used cyclohexane, ethyl acetate and water-saturated n-butanol to get four different extraction parts. The anti-inflammatory activity of different extracted parts ofK.striata(Thunb.) Schindl. was evaluated by the acute inflammation model of mouse ear swelling induced by classical xylene. The results showed that the ethyl acetate extract ofK.striata(Thunb.) Schindl. could significantly inhibit xylene-induced auricle swelling in mice compared with the negative control group, and had the same anti-inflammatory effect as the positive drug aspirin group, suggesting that there were active components which could effectively inhibit the release of inflammatory factors in the ethyl acetate extract ofK.striata(Thunb.) Schindl. In addition,K.striata(Thunb.) Schindl. could significantly inhibit the increase of celiac capillary permeability induced by acetic acid and resist the writhing response induced by acetic acid in mice. At the same time,K.striata(Thunb.) Schindl. could also significantly reduce the pain caused by chemical stimulation and thermal stimulation caused by xylene, and inhibit the proliferation of cotton granulation tissue and connective tissue in the late stage of inflammation in mice[13]. Tao Junyanetal. published a report on the anti-inflammatory mechanism of ethanol extract ofK.striata(Thunb.) Schindl. in the journal Inflammation. The results showed that the ethanol extract ofK.striata(Thunb.) Schindl. down-regulated the expression of iNOS, COX-2 and TNF- α genes by inhibiting the activation of NF-κB in RAW264.7 cells induced by lipopolysaccharide, and then decreased the expression of inflammatory factors NO, IL-1β and TNF-α, and reduced the occurrence of inflammation[14]. This report illustrated the clinical application ofK.striata(Thunb.) Schindl. in inflammatory diseases at the mechanism level.

3.2AntioxidantstressinjuryThe extraction parts of different flavonoids such as petroleum ether, chloroform, ethyl acetate and n-butanol from ethanol extract ofK.striata(Thunb.) Schindl. have significant scavenging effect on hydroxyl radical (OH·) and superoxide anion, so they are a kind of natural antioxidants[15]. Apigenin is a kind of common flavonoids naturally found inK.striata(Thunb.) Schindl., which has low toxicity and no mutagenicity. In recent years, a large amount of literature[16-18]has reported that apigenin has a variety of pharmacological activities, including anti-tumor activity, cardio-cerebrovascular protection, anti-inflammatory, antioxidant, antiviral effects. Huang Binetal.[19]reported the results of apigenin in improving renal oxidative stress injury in obese rats; under some special physiological and pathological conditions, such as obesity, hyperinsulinemia and hyperlipidemia, the production of a large number of reactive oxygen species in the body or the decrease of antioxidant defense ability of the body would lead to oxidative stress, resulting in damage to important target tissues and organs of the whole body. Take ischemic and hypoxic diseases such as myocardial infarction and stroke caused by coronary arteriosclerosis for example, after the sudden restoration of blood supply, the body was in a state of oxidative stress, which would produce a large number of oxygen free radicals, resulting in tissue ischemia-reperfusion injury. The results of Huang Binetal. found that apigenin could significantly reduce the level of reactive oxygen in rat kidney cells and effectively improve the oxidative stress and inflammation of rat kidney caused by obesity. It has been reported thatK.striata(Thunb.) Schindl. has a definite effect in the treatment of hematuria and glomerulonephritis proteinuria. The research of Wang Xiaetal.[20]showed that the treatment effect ofK.striata(Thunb.) Schindl. on IgA nephropathy might be related to its ability to improve microcirculation and hemorheology, scavenge free radicals and increase the activity of antioxidant enzymes. Their research reports showed that the water extract ofK.striata(Thunb.) Schindl. could enhance the blood flow velocity of auricular arterioles in mice, improve blood microcirculation, significantly reduce the whole blood viscosity, improve the hemorheology of rats, significantly reduce the contents of blood urea nitrogen (BUN), creatinase (SCR), and malondialdehyde (MDA) in serum of model rats, increase the activity of superoxide dismutase (SOD), scavenge free radicals and increase antioxidant activity. It can be concluded thatK.striata(Thunb.) Schindl. plays a positive role in dilating glomerular capillaries, increasing renal blood flow, improving hemorheology and reducing glomerular damage in the treatment of IgA nephropathy.

3.3HemostaticeffectZhou Jiuyaoetal.[21]reported the hemostatic effect ofK.striata(Thunb.) Schindl. in the study of its hemostatic effect. Mice were given intragastric administration of different doses of water extract ofK.striata(Thunb.) Schindl. (each 100 mL of concentrate is equivalent to 80 g of original drug) for 14 d. The clotting time, bleeding time and platelet count were measured respectively. The results showed that the water extract ofK.striata(Thunb.) Schindl. could significantly shorten the bleeding time of mice, increase the role of platelet, thus playing a hemostatic effect. It can be seen that the water extract ofK.striata(Thunb.) Schindl. must contain some water-soluble active substances that can effectively participate in the regulation of any link of the blood coagulation function of the body, such as the content and activity of coagulation factors in the blood system, the function of capillaries, as well as the number and function of platelets, so as to cause the body to produce blood clotting reaction.

3.4Anti-tumoractivitySo far, malignant tumor is still the most difficult major disease in the world, seriously endangering human life and health, and ranks second in the mortality rate of all diseases[22]. The search for new antineoplastic drugs is still a hot topic. In the experiment of antitumor activity of quercetininvitro, Xu Haoetal.[23]found that quercetin nano-suspension could effectively solve the problem of poor water solubility of quercetin, improve the drug stability, and significantly inhibit the growth of mouse breast cancer cell line 4T1, cervical cancer HeLa cell and hepatoma HepG2 cell. Among them, 4T1 cell was most sensitive to quercetin nano-suspension. In addition, the experimental results of transplanted tumor showed that quercetin nano-suspension still had an effective anti-breast cancer effectinvivo. It can be concluded that quercetin is not only a kind of flavonoids widely distributed in nature, but also a kind of flavonoids isolated and extracted fromK.striata(Thunb.) Schindl., which has a wide range of pharmacological activities. From the relevant literature, there are few studies on the anti-tumor activity ofK.striata(Thunb.) Schindl. Therefore, this will be a subject worthy of further study in the future.

3.5AntiviraleffectThe dried whole grass ofK.striata(Thunb.) Schindl. has long been used for the treatment of cold and fever, summer-heat and dampness, vomiting and diarrhea, dysentery and other diseases. A large amount of literature has reported that the active components of flavonoids and glucosides inK.striata(Thunb.) Schindl. have the effects of clearing heat and detoxification, invigorating the spleen and promoting dampness. Sun Haoetal. have carried out a lot of studies on the therapeutic effect ofK.striata(Thunb.) Schindl. on infantile rotavirus enteritis[6]. We treated 110 cases of rotavirus-positive children withK.striata(Thunb.) Schindl., and achieved good clinical results, the treatment effective rate reached 92.2%, with no obvious side effects[7]. In addition, it is recorded in National Compendium of Chinese Herbal Medicine thatK.striata(Thunb.) Schindl. is also used in the treatment of hepatitis and is also used in clinical practice. It can be seen thatK.striata(Thunb.) Schindl. has a good application prospect in antivirus, but the specific molecular mechanism and active material basis of its antivirus are not clear. Based on this research background, some researchers have studied the role ofK.striata(Thunb.) Schindl. in resisting HIV virus. In 1994, Tang Renjiu[24]published an article in the British Journal of Organic Chemistry and Pharmaceutical Chemistry to study apigenin-7-O-β-D-glucoside extracted fromK.striata(Thunb.) Schindl. as a new anti-HIV drug. In searching for new anti-AIDS drugs, we found four flavonoids extracted from leguminous plantK.striata(Thunb.) Schindl., namely apigenin, quercetin, kaempferol-3-O-ED-glucopyranoside and apigenin-7-O-neohtxperidoside. The inhibitory effects of these four flavonoids on P24 antigen in the supernatant of T cells infected with HIV were detected by ELISA assay. It was found that apigenin-7-O-β-D-glucoside showed good anti-HIV activity compared with other flavonoids and positive drugs, and thus the application ofK.striata(Thunb.) Schindl. in resisting HIV virus was found. Through this research report, the antiviral mechanism ofK.striata(Thunb.) Schindl. was expounded at the molecular level, which put forward a new direction for the study of the pharmacological activity ofK.striata(Thunb.) Schindl.

3.6AntibacterialactivityFlavonoids are a kind of important natural organic compounds widely existing in nature, which have important physiological activities, including antioxidant, anti-inflammatory, anti-allergic, anti-tumor and antibacterial activities[25-26]. Flavonoids are also one of the most important active components inK.striata(Thunb.) Schindl. Luteolin-7-glucoside has the effect of clearing heat and detoxification, invigorating the spleen and removing dampness. The water extract ofK.striata(Thunb.) Schindl. has a certain antibacterial effect on Flexner’s dysentery and Shigella dysenteriae and so oninvitro[9], so it is often used to treat bacterial enteritis, diarrhea and other diseases in clinic.

4 Discussion

Most natural flavonoids have obvious physiological activities, such as lowering blood pressure, lowering blood lipids, antiviral, anti-inflammatory, antioxidant, anti-tumor and antibacterial effects. To sum up,K.striata(Thunb.) Schindl. is a kind of important variety with wide application prospect, which contains many kinds of active substances, such as flavonoid glycosides, sterols, amino acids, and polyphenols. However, according to the current literature, the research ofK.striata(Thunb.) Schindl. is mainly focused on the antioxidation, anti-inflammation and analgesia of flavonoids. The research area is narrow, and it is not systematic and deep. The study of activity is mainly focused on macropharmacology, but not on toxicology, molecular pharmacology, pharmacokinetics and so on. In addition, there is only an in-depth study on the structure of flavonoids in the chemical constituents ofK.striata(Thunb.) Schindl. Amino acids, sterols, polysaccharides and phenols also play an important role in the pharmacological activity ofK.striata(Thunb.) Schindl. However, due to the limited number of compounds extracted and isolated fromK.striata(Thunb.) Schindl., the basis of active substances is not clear, and from 2000 to now, there is still no new breakthrough in the research ofK.striata(Thunb.) Schindl. To sum up, only by a clear understanding of the chemical composition and material basis ofK.striata(Thunb.) Schindl. can we better study and discover its activity, and then reveal its pharmacological mechanism step by step at the molecular level, to provide a strong basis for rational clinical use, and also provide a reference for the research and development of new drugs.