Advances in Research of Chemical Components and Pharmacological Effects of Platycladus orientalis Leaves

Ruifeng ZHANG, Yang ZENG, Likuan LIU, Hongyu WANG, Wenming ZUO, Junyan ZHANG, Jinping LI

College of Life Sciences, Qinghai Normal University / Key Laboratory of Medicinal Animal and Plant Resources on the Qinghai-Tibet Plateau, Xining 810000, China

Abstract Platycladi Cacumen (Platycladus orientalis leaf) is a traditional Chinese medicine with a variety of medicinal values, and its efficacy has been recorded by many ancient books. Its chemical components mainly include flavonoids, volatile oil, tannins and so on. Pharmacological studies have confirmed that P. orientalis leaves have various pharmacological effects such as antibacterial, anti-oxidant, anti-tumor, hair growth promoting and hemostatic effects. Through review of the research on the chemical components and pharmacological effects of P. orientalis leaves, this study is intended to provide reference for the research, development and utilization of P. orientalis.

Key words Platycladus orientalis, Platycladi Cacumen, Chemical components, Pharmacological effects

1 Introduction

As a plant of the genusPlatycladusin the Cupressaceae family,Platycladusorentalis(L.) Franco is widely distributed in China, mainly in southern Inner Mongolia, Liaoning, Yunnan, Hubei provinces; it is also found in the Lancang River Basin in Yunnan Province, the Weihe River Basin north of the Qinling Mountains in Shaanxi Province, and Xinglong in Hebei Province[1].Platycladusorentalisis unique plant of China. Its leaves are small scaly leaves, affixed to flat branches, alternately opposite, dark green or yellow-green, brittle and easy to break, yellow-white in section[2]. According to literature records,P.orientalisleaves have a fragrant smell and a bitter taste, belong to the lungs, liver and spleen meridians,P.orientalisleaves have the effects of relieving cough, reducing phlegm, promoting hair growth, and the hemostatic effect ofP.orientalisis suitable for various bleeding diseases[3].P.orientalisleaves contain many types of medicinal active components, among which flavonoids, volatile oils, and tannins have been studied;P.orientalisleaves have antibacterial, anti-tumor, hemostasis, hair growth promotion, anti-inflammatory and other pharmacological effects. The potential medicinal value ofP.orientalisleaves and clinical auxiliary effects on various diseases have become increasingly obvious. We further summarized the chemical components and pharmacological effects ofP.orientalisleaves, hoping to provide a scientific theoretical basis for future research.

2 Chemical components

2.1 FlavonoidsAt present, the research of flavonoids in the chemical components ofP.orientalisleaves is the most. In addition to the quercetin specified in thePharmacopoeia, the known flavonoids inP.orientalisleaves contain myricitin, rutin, kaempferol, and amentoflavone[4-6]. Flavonoids and diflavonoids are not only characteristic components, but also effective components of ofP.orientalisleaves. Meng Lijuanetal.[7]used myricitin, quercetin, hinokiflavone and amentoflavone as indicators for quality control ofP.orientalisleaves. Common methods for extraction of flavonoids fromP.orientalisleaves include enzyme extraction, water extraction, reflux extraction, ultrasonic extraction, and microwave extraction[8]. Using ultra-high performance liquid chromatography-mass spectrometry technology, Shan Mingqiuetal.[9]identified 11 flavonoids in theP.orientalisleaves and made a further study and found that the combined method of ultra-high performance liquid chromatography and electrospray mass spectrometry is rapid and efficient in the identification of the flavonoids. Qiu Silanetal.[10]used the reflux method to extract the total flavonoids fromP.orientalisleaves, and found that the extraction rate was 1.672 8% under the optimal extraction process conditions. Other studies have found that the use of ultrasonic assisted extraction of total flavonoids fromP.orientalisleaves can shorten the extraction time and increase the extraction rate[11]. In addition, combination of homogenization method and ultrafiltration membrane can effectively improve the purification rate of flavonoids inP.orientalisleaves, and the method has high feasibility and high product purity[12].

2.2 Volatile oilCompounds in the volatile oil ofP.orientalisleaves are mainly divided into monoterpenes, sesquiterpenes and aliphatic hydrocarbons[13], among which monoterpenoids and sesquiterpene compounds are the basis of the pharmacological activities ofP.orientalisleaves. There are many factors that affect the difference in the content of volatile oil fromP.orientalisleaves, such as region, test process and picking time[14-17]. At present, studies have found that the volatile oil components ofP.orientalisleaves are mainly α-caryophyllene, β-caryophyllene, α-pinene, 3-carene, limonene, cedarol, cinderol, and terpineol acetate[18-21]. Common extraction techniques for volatile oil fromP.orientalisleaves include enzyme extraction, simultaneous distillation extraction and steam distillation-extraction; GC-MS is a commonly used method for the analysis of volatile components inP.orientalisleaves[22]. Zhou Wei[23]used GC-MS to analyze the chemical components of the 21 volatile oils ofP.orientalisleaves, and 14 of them were terpenoids and their derivatives. Yang Huaetal.[17]used ultrasonic-assisted steam distillation to extract the volatile oil ofP.orientalisleaves. They separated more than 60 components and GC-MS analysis identified 21 compounds, accounting for 80.15% of the total volatile oil. Moreover, Menggenqiqigeetal.[24]compared the two processes of steam distillation and microwave extraction to extract the essential oil ofP.orientalis. They determined the optimal extraction process conditions of microwave extraction as follows: power was 1 800 W, time was 30 min, solid-to-liquid ratio was 20∶1 (mL/g), and the extraction rate of essential oil was 4.02%, while the extraction rate of traditional steam distillation was only 1.3%, the microwave extraction process can significantly increase the extraction rate of the essential oil ofP.orientalisleaves (an increase of 2.72%).

2.3 TanninsTannin compounds are polyphenols with complex structures in plants. Zeng Xianglietal.[25]used the method specified inPharmacopeiaofthePeople’sRepublicofChinato determine the tannin content ofP.orientalisleaves and the raw tannin content was 0.268 0% and the charcoal tannin content was 0.143 4% and concluded that this method can be used for the determination of the tannin content ofP.orientalisleaves raw and charcoal products. Cheng Lifangetal.[26]found that the casein method is suitable for the determination of tannin content inP.orientalisleaves, and this method has high selectivity. The common extraction processes for tannins include dipping, homogenization extraction, hot reflux extraction, supercritical fluid extraction, ultrasonic extraction, and semi-bionic extraction,etc[27-28]. At present, there are few reports on the activity of tannins at home and abroad. In recent years, with the continuous progress of science and technology, the research of tannin compounds has received wide attention.

2.4 Other componentsIn addition to the above chemical components, there are other chemical components in the leaves ofP.orientalis, but their content is relatively small, such as inorganic elements[29], organic acids[30]and polysaccharides[31]. Among them, the polysaccharide components ofP.orientalisleaves include glucose, mannose, arabinose, galactose, rhamnose,etc[32].

3 Advances in pharmacological studies

3.1 Antibacterial effectsMany researchers have found thatP.orientalisleaf extract has good antibacterial activityinvitro. It has the most obvious inhibitory effect onStaphylococcusaureus,Escherichiacoli,EnterobacteraerogenesandMicrococcustetragenus, but the inhibitory effect on Bacillus subtilis is not obvious[33]. According to some study[34], the antibacterial effect ofP.orientalisleaves may be related to the tannin compounds. Using the agar plate and filter paper diffusion method, Zhou Wei[23]studied the antibacterial activity ofP.orientalisleaf extract against several common bacteria in food, and found that its extract has strong antibacterial activity againstBacillusthuringiensisandS.aureus. Song Jin[35]found that the minimum inhibitory concentration (MIC) of the purifiedP.orientalisleaf extract againstStreptococcusmutanswas 37.5 mg/mL, and the flavonoids inP.orientalisleaves may be the main inhibitor of S. mutans. Chen Xingfenetal.[36]found that the volatile oil ofP.orientalisleaves had obvious inhibitory effect on three common fungi, Aspergillus niger, Penicillium and Rhizopus, and its minimum inhibitory concentration (MIC) was 25.00, 25.00, and 12.50 mg/mL, respectively. Zhou Zhongjie[37]found that the extract ofP.orientalisleaves had a strong inhibitory effect on the two negative bacteria ofE.coliandXanthomonascampestris. Zhu Bin[38]found that the extract ofP.orientalisleaves has a good inhibitory effect onColletorichumlagenerium,Sclerotiniasclerotiorum,Fusariumgraminearum, andFusariumoxysporum, the inhibition rate was up to 50%; it also has 45%-50% inhibition againstColletotrichumcapsici, andAlternariasolani.

3.2 Anti-inflammatory effectsAccording to findings of Tang Jieetal.[39], the extract ofP.orientalisleaves can repair the SOD activity of HaCaT cells damaged by SDS and inhibit the secretion of inflammatory factors in the supernatant of RAW264.7 cells. Li Lietal.[40]found thatP.orientalisleaf decoction has anti-acute inflammation effect on auricle inflammation and abdominal cavity inflammation model mice, and its mechanism may be related to the reduction of TNF-α, IL-1 and ASIC1a factors. Liang Tongetal.[41]found that the alcohol extract ofP.orientalisleaves contains strong anti-inflammatory components, and its action mechanism of action is related to the inhibition of the metabolism of arachidonic acid. Further studies have found that its extract can inhibit the biosynthetic pathway of platelet 12 hydroxy heptadecatrienoic acid.

3.3 Antioxidant effectsExtensive studies have found thatP.orientalisleaf extract has antioxidant properties. Li Yuanhuietal.[42]measured the ability ofP.orientalisleaf polysaccharides to scavenge superoxide anion free radicals, and found that when the polysaccharide concentration was 0.5 g/L, its scavenging rate was as high as 72.97%, indicating that its polysaccharides have antioxidant capacity. Wang Miaomiaoetal.[43]found thatP.orientalisleaf extract has a strong inhibitory effect on 5α-reductase in the liver and epididymis, and the antioxidant content of the extract has a certain correlation with DPPH free radical scavenging rate and total antioxidant capacity; further research found that the content of flavonoids and polyphenols inP.orientalisleaves is relatively high, and the antioxidant capacity is also relatively high. Ding Hangetal.[44]proved that flavonoids can effectively inhibit the hemolysis and lipid peroxidation of human red blood cells caused by hydrogen peroxide. Zhou Yufanetal.[45]found that the volatile oil ofP.orientalisleaves can effectively inhibit the chelation of phenazine and Fe2+(IC50value was 0.409 mg/mL) and the oxidation of β-carotene-linoleic acid (IC50value was 0.526 mg/mL). Li Xueetal.[46]found that the ethanol extract ofP.orientalisleaves had a significant dose-effect relationship on the scavenging ability of hydroxyl radicals and superoxide anion free radicals; when the mass concentration was greater than 0.5 mg/mL, the 50% ethanol extract had the strongest scavenging ability for hydroxyl radicals.

3.4 Anti-tumor effectsMiao Hui[22]studied the anti-tumor activity of crude polysaccharides ofP.orientalisleaves on H22mouse subcutaneous xenograft tumor model, and the results showed that crude polysaccharides ofP.orientalisleaves can achieve anti-tumor effects mainly by improving the body’s immunity and antioxidant capacity. Using the Alamarblue method, Jiang Jihongetal.[47]conducted an anti-human lung cancer cell experiment on the extract ofP.orientalisleaves and found that its volatile oil has a strong inhibitory rate on lung cancer cells NCI-H460, and cedrol is the main active component of anti-lung cancer cells.

3.5 Hemostatic effectsIn ancient books, there were records that the quercetin inP.orientalisleaves has hemostatic function. Modern medical research has found that the charcoal ofP.orientalisleaves also has hemostatic effects. Chen Chaoetal.[48]found thatP.orientalisleaves should be processed as hemostatic medicines in clinical applications, and the hemostatic effect ofP.orientalisleaves was significantly enhanced after charcoal frying. The main active component of the hemostatic effect of its decoction production is total flavonoids. Using the analytic hierarchy process (AHP), Song Jinetal.[49]established an in vitro comprehensive hemostatic evaluation model to screen Chinese herbal medicines with good hemostatic effects and the model showed thatP.orientalisleaves had a good hemostatic effect. Liu Chenetal.[50]found thatP.orientalisleaves raw and charcoal products had a certain hemostatic effect on blood-heat combined hemorrhage model rats, and the charcoal product had a better hemostatic effect, and the possible mechanism is that it acts on the endogenous coagulation pathway to improve the coagulation function, and enhance the prevention and suppression of pathological injuries such as pulmonary hemorrhage.P.orientalisleaves also play an important role in the compatibility of traditional Chinese medicines. According to the research of Liang Zhenyuetal.[51], the compatibility ofP.orientalisleaves and Baiye Decoction has a good hemostatic effect on gastric hemorrhage model rats with spleen and stomach deficiency and cold, and the mechanism may be that it affects platelet aggregation and shortens the clotting time to achieve hemostatic effect, and inhibits the formation of gastric ulcers by enhancing gastric mucosal microcirculation.

3.6 Hair growth promotionAccording to records ofCompendiumofMateriaMedica,P.orientalisleaves have a significant effect on the treatment of hair loss. Modern studies have confirmed that the main effective component ofP.orientalisleaves in the treatment of hair loss is flavonoid extract[52], andP.orientalisleaf tincture can be used to treat hair loss and is generally used externally. Lei Meng[18]found that the volatile oil ofP.orientalisleaves can induce the expression of β-catenin protein in mouse hair follicle cells, thereby promoting hair follicle regeneration, and clarified the mechanism of the volatile oil ofP.orientalisleaves to promote hair growth. According to the findings of Miao Hui[22], isoprerenol and pinusolide inP.orientalisleaves can enhance the vitality of hair follicles, maintain the normal growth of hair follicles, and promote hair growth, and the mechanism of action is related to the content of VEGF in the serum. Zhang Bei[53]found that the ethanol extract ofP.orientalisleaves can promote the growth of hair follicles and inhibit hair follicles from the growth phase to the resting phase, thereby promoting hair growth. Shan Chengyingetal.[54]found that the volatile oil ofP.orientalisleaves has the effect of promoting hair growth, and further explored and found that the alcohol extract and volatile oil ofP.orientalisleaves can delay hair loss.

4 Prospects

In conclusion,P.orientalisis a widely distributed and unique tree species in China. Due to its rich chemical components and high medicinal value, it has received extensive attention. Studies have confirmed that different production areas and different seasons of the year will cause differences in the chemical components and content ofP.orientalisleaves. The content of some active components ofP.orientalisleaves is extremely low, and the separation and functional research are extremely difficult. Many factors increase the difficulty of the research of its chemical components.P.orientalisleaves have a variety of pharmacological effects such as antibacterial, anti-tumor, hemostatic effects and promotion of hair growth. However, the pharmacological mechanism of action is still unclear, and there are relatively few studies on toxic and side effects. Therefore, it is necessary to make in-depth study, to ensure the safety of clinical medicine.